ANALGESICS

ANALGESICS I. Opioid (narcotic) analgesics 1. Agonists of opioid receptors – morphine

hydrochloride, promedol, omnopon, fentanil, codeinн;

2. Agonists – antagonists and partly agonists of opioid receptors – pentasocin, buprenorphine.

II. Nonnarcotic analgesics and nonsteroid antiinflammatory drugs

acetysalycylic acid, paracetamol, analgin, indometacin, butadion, ibuprofen, pyroxicam, diclofenac-sodium, ketorolac, ketoprofen.

III. Substances with mixed mechanism of action (opioid and nonoioid components)

tramadole

NARCOTIC

ANALGESICS

The following structures take part in

perception of pain: thalamus, hypothalamus, reticular formation, limbic system, occipital and frontal areas of cortex

System which conducts and perceives pain - nociceptive

System which contracts pain – antinociceptive

Visceral pain – from internal organs

Somatic pain – bones, muscles, articulations, teeth,

ligaments, nerves

Opioid system Contents:

• opioid receptors

• endogen opioid substances – endorphins, encephalines, dinorphines

Subtypes of opioid receptors:

mu, delta, kappa, epsilon, sigma

Subtypes of opioid receptors

mu

Analgesia, depression of breathing, euphoria, addiction development, sedative effect, depression of contents mocing through digestive tract, miosis

kappa Analgesia, sedative eefect, psychotomimetic action

delta Analgesia, euphoria, behaviour chnages

sigma Mania, increasing of breathing frequency, hallucinations, midriasis

Poppy

1. Papaver

rhoeas L.

2. Papaver

somniferum L.

2 1

Morphine hydrochloride “mosaic action” on central nervous system

Effects of depression • analgesia

• decreasing of frequency and depth of breathing

• depressing of central links of coughing reflex

• from the side of psychic sphere – somnolence, retardness

Effects of stimulation • vomiting (excitation of trigger zone of vomiting center)

• bradycardia (increasing of tone of vagal nerve nuclei)

• miosis (increasing of tone of n. oculomotorius nuclei)

• euphoria (condition of full psychological wellness with pleasant emotional feelings and feeling of physical comfort)

• increasing of activity of spinal cord intermediate neurons

ADMINISTRATION OF NARCOTIC

ANALGESICS

• prophylaxis and treatment of pain shock • traumas • burns • acute myocardium infarction • premedication for potentiation of action of narcosis

drugs, analgesia in postoperative period • colics • to releive sufferings of oncologic patients of 4

clinical group (can’t be treated radically) • acute abdomen (strong pain in abdominal cavity,

caused by perforation of ulcer, acute appendicitis, acute intestinal impassability etc.) – only from the moment then diagnosis becomes clear

MORPHINE HYDROCHLORIDE

Ways of introduction into organism • subcutaneously and intramuscularly (analgesic action after 10-15 min) • after oral introduction – presystemic

elimination ( 20-60 % enters general blood circulation) • sublingually – quick absorption • into epidural, subarachnoic spaces • into brain ventricles

Duration of analgesic action – 4-6 hours Maximal one-time dose of morphine is 0,02 g,

maximal day dose – 0,05 g

Side effects of morphine

•addiction • tolerance • vomiting (excitation of starting zone of

vomiting center) • bradycardia (increasing of tone of n. vagus

nuclei) • spasm of sphincters of gastro-intestinal tract

accompanied by constipations • increasing of tone of smooth musculature of

urinary and bile-excreting tracts (retentions of urination, bile stasis)

• Bronchial spasm

CONTRAINDICATIONS FOR ADMINISTRATION OF

MORPHINE

pain that accompanies chronic diseases. In exceptional

occasions it is introduced (not more than 1-2 injections) in

case of pain which threatens development of pain shock, for,

example, acute attach of ulcer disease

children before the age of 2 years

for aged from 2 to 6 years and elderly the drug should be

administered very carefully (breathing depression is possible)

pregnancy and lactation

anesthesia during child delivery (fetus breathing depression)

skull traumas, brain hemorrhages (increasing of intracranial

pressure)

depression of function of breathing center, damage of

respiratory organs, bronchial asthma

OMNOPON contains mixture if opium alkaloids

(48-50% morphine)

does not cause spasms of smooth

musculature, as it contains alkaloids of

isochinoline raw

is used for analgesia according to all the

indications of morphine hydrochloride, for

example, colics

Promedol duration of analgesic action - 3-4 hours

moderate spasmolytic influence on smooth

musculature of internal organs

stimulation of rhythmic contractions of

uterus

does not depress breathing

can be used for analgesia and stimulation

of child delivery

in case of pain syndrome connected with

spasms of smooth musculature

Phentanil synthetic narcotic analgesic of short action

analgesic activity is 300 times higher than of

morphine

analgesic effect after intravenous introduction –

after 1-3min, lasts for 15-30min

used with a narcoleptic droperidol (complex

drug – “talamonal”) for neuroleptanalgesia – a

variant of general anesthesia

Codeine opium alkaloid

analgesic action is not strong, but

anticough effect is considerable

administered as an anticough drug of

central action

analgesic with weak activity combined with

non-narcotic analgesics (paracetamol) for

potentiation of the effect

Pentazotsin agonist-antagonist of opioid receptors

it is a bit less dangerous in the aspect of addiction

development (in comparison with morphine)

indicated in case of pain of medium intensity in

such conditions like other narcotic analgesics.

it can cause increasing of blood pressure and

tachycardia that’s why it’s not advised to use in

case of acute myocardium infarction

if it is administered for people with narcotic

addiction manifestations of abstinence develop

Buprenorphine Partly agonist of mu-opioid receptors

Acts longer than morphine (approximately 6 hours)

Analgesic activity is higher than of morphine, that’s

why it’s used in doses of 0,3-0,6 mg

Indicated for pain decreasing in the same situations

as other narcotic analgesics

May be used for detoxication and supporting

treatment of individuals who is addicted to heroine

TRAMADOL

Analgesic activity is not weaker than activity of morphine

In case of intravenous administration effect develops after 5-10 min,

if administered orally – after 30-40 min, action lasts for 3-5 hours.

ADMINISTRATION OF TRAMADOL

surgery, traumatology, gynecology,

neurology, urology, oncology

For all kinds of acute and chronic pain of

moderate and considerable intensity,

including postoperative, traumatic pain!

neuralgias

diagnostic and therapeutic interventions

oncologic pathology

Acute poisoning with narcotic analgesics

It is often observed in drug addicts death – from breathing depression

SYMPTOMS

dizziness

nausea, vomiting (rarely), heavy sweating

general weakness, somnolence, which after transfers into deep dream and coma

pale and cyanotic skin, decreased body temperature

weak pulse, decreased blood pressure

rare and superficial breathing

Triad in case poisoning with morphine

Acute miosis

Pathological breathing of Chain-Stocks’ type

Saved tendon reflexes

Treatments of acute poisoning

Naloxon (antagonist of opium receptors)

i.v.- 0,4-1,2 mg

stomach lavage (for morphine enterohepatic

circulation is typical) with 0,05-0,1% solution of

potassium permanganate and 0,5 % tannin solution

salt laxative agents (sodium sulfate)

forced diuresis

atropine sulfate

inhalation of carbogen (5-7 % СО2 and 93-95 % O2)

All narcotic analgesics cause

drug addiction – narcomania

Manifestations

psychological dependence

physical dependence tolerance

abstinence syndrome

NON-NARCOTIC

ANALGESICS

Types of action of non-narcotic analgesics

•Analgesic

•Antipyretic

•Anti-inflammatory

(except paracetamol)

Mechanism of action of non-narcotic

analgesics depression of cyclooxygenases activity

decreasing of prostaglandins synthesis in

peripheral tissues and in central nervous

system

decreasing of sensitivity of nervous endings

and depression of transduction of

nociceptive impulses on the level of CNS

structures

pain-relieving action of non-narcotic

analgesics is partly connected with their

anti-inflammatory activity

Indications for administration of

non-narcotic analgesics

headache

toothache

radiculitis

neuritis, neuralgias

myositits, myalgia

arthritis, arthralgia

pain, connected with pelvic organs (dysmenorrhea)

for potentiation of their action – combinations paracetamol with codein, analgin with dimedrol, analgin with codein

Acetylsalicylic acid

Blocks cyclooxygenase

irreversably

As a pyrolytic and analgesic drug –

0,25 and 0,5 g per time

As an antiinflammatory – 3-4 g per

day (for arthritis, myocarditis,

pleuritis, bronchitis etc.

For prophylaxis of thrombus-

formation (in case of ischemic

heart disease, thrombophlebitis

etc.) – daily dose – 80-100 mg

Analgin (metamizol-sodium)

Baralgin (maxigan, spazgan, spazmalgon, trigan) analgin+pitophenon hydrochloride+pheniverinium bromide

•Ampoules tablets suppositories •Analgesic and

spasmolytic activity

Paracetamol analgesic and antipyretic drug

maximal effect if the drug is introduced

orally – after 2 hours, lasts approximately

for 4 hours

in case of durable administration of big

doses – damaging of liver and kidneys,

production of met-hemoglobin

Paracetamol

Tablets

Suppositories

Syrups

Soluble tablets

Capsules

PARACETAMOL

Panadol (paracetamol)

Ketorolak (ketanov) according to analgesic activity it prevails over

effect of acetylsalicylic acid, indometacin and

equals to opioid analgesics

moderate anti-inflammatory, antipyretic and

anti-aggregate effects

high effectiveness in case of pain in

postoperative period, in oncology, during

child delivery, traumas, colics

intramuscular introduction, orally

Analeptics are general CNS stimulants; they

stimulate vitally important centers

(respiratory and vasomotor) of the brain.

Analeptics

CLASSIFICATION OF ANALEPTICS UNDER

THE MECHANISM OF ACTION:

1. DIRECT-ACTING drugs, which stimulate centers of

the medulla oblongata:

Bemegride, Aethymizole, Caffeine 2. REFLECTORY-ACTING: cause reflectory timulation

of the respiratory center due to H-cholinoreceptors

of the sinus caroticus stimulation.

Cytitonum, Lobelinum 3. MIX-ACTION ANALEPTICS: They act as directly on

the respiratory and vaso-motor centres, as

reflectory on the chemoreceptors of vessels.

Cordiamine, Camphor, Sulfocaphocaine

CLASSIFICATION UNDER THE

INFLUENCE ON THE DIFFERENT

PARTS OF THE CNS:

Analeptics, act mainly on the cortex of the

brain: Caffeine

Analeptics, act mainly on the subcortex

centers: Bemegride, Aethymizole, Cytitonum,

Lobelinum, Cordiamine, Camphor,

Sulfocaphocaine

Analeptics, act mainly on the spinal cord:

Strychninum

INDICATIONS FOR USE OF

ANALEPTICS:

Hypoxias, respiratory failure

Overdosing or poisoning with narcotic drugs,

general anesthetics, alcohol, hypnotic drugs

To speed up awakening action after narcosis

Asphyxia of newborns;

Shocks, collapses

Prophylaxis of lung atelectasis and pneumonia

SIDE EFFECTS OF ANALEPTICS:

Nausea, vomiting

Sezures

Increasing of reflex excitation

Hyperventilation

Cardiac arrythmia

PSYCHOMOTOR STIMULANTS

PSYCHOMOTOR STIMULANTS

Derivatives of purine – caffeine

Phenilalkilamines – phenamine

(amphetamine)

Phenilalkilsydnonimins -

sydnocarb

Properties of psychomotor

stimulants

Stimulate intellectual activity, speed up thinking processes, temporarily eliminate tiredness, somnolence

Eliminate such manifestations of neurosis as: subdepression, fatigue, retardness

Aren’t able to eliminate endogen depression, which accompanies psychic diseases

Caffeine

Mechanism of action

• Binding with adenosine (“purine”) receptors

in brain (endogen ligand of these receptors –

adenosine decreases processes of excitation

in CNS)

• Inhibiting of phosphodiesterase, which leads to

accumulation of cAMP and stimulation of many

physiological processes and metabolism

Usage of phychostimulating

influence of caffeine

For stimulation of psychological

processes, workability, to eliminate

somnolence

Enuresis, narcolepsy

In case of poisoning with alcohol

To speed up awakening after narcosis

Influence of caffeine on cardiac-

vascular system Vessels

1. Stimulation of vasomotor center – contraction of vessels, increasing of AP

2. Peripheral myotropic spasmolytic action – dilation of vessels, decreasing of AP

Heart 1. Central action (increasing of n. vagus

tone) – bradycardia

2. Peripheral action (direct influence on heart) – tachycardia, possible extrasystolia

Influence of caffeine on cardio-

vascular system

Contraction of brain vessels

Dilation of kidney vessels, increasing of

diuresis

Dilation of coronary vessels

In case of depression of centers of brain

stem (medulla oblongata) caffeine

shows stimulating properties, increases

blood pressure, stimulates breathing –

analeptic action

SIDE EFFECTS OF CAFFEINE

If administered regularly – psychological

addiction – theism, which is accompanied by

development of abstinent syndrome

(retardness, fatigue, somnolence, depression)

Tolerance

Teratogenic action (inborn abnormalities)

Increasing of frequency of stenocardia,

hypertension

Acute attacks of ulcer disease (it increases

gastric secretion)

Acute poisoning in case of overdosing

NOOTROPIC DRUGS (NEUROMETABOLIC CEREBROPROTECTORS)

Neurometabolic cerebroprotectors

Derivatives of pyrrolidone – pyracetam (nootropil)

Derivatives of GABA – aminalon, Na oxybutyrate

Neuropeptides – melatonin, sinacten-depot

Cerebrovascular drugs – sermion (nicergolin),

cavinton (vinpocetin), stugeron (cinnarisin),

pentoxyphylline (trental), xantynole

nicotinate

Derivatives of piridoxine – piritinol (encephabol)

Antioxidants – mexidol, tocopherole acetate

Others – cerebrolysine, actovegin, solkoseryl,

plant preparations

Properties of nootropic drugs

Improvement of brain blood circulation,

promotion of collaterals development

Psychostimulating effect, antiasthenic action

Sedative, antidepressive action

Antiepileptic, antiparkinsonic action

Nootropic action

Mnemotropic action

Vasovegetative action

Antihypoxic action

Administration of nootropic drugs

Atherosclerosis of brain, vascular parkinsonism,

Alzheimer's disease

Disorders of brain blood circulation in case of traumas

and intoxications, vascular diseases of brain

Diseases of CNS, accompanied by decreasing of

intellect, memory

Disorders of psychology (in elderly with schizophrenia,

depressions)

To decrease manifestations of abstinence (alcoholism,

drug addiction)

In neurology (neurasthenia, migraine, neuralgias,

radiculitis)

In pediatrics in case if mental insufficiency

Piracetam (nootropil)

Cerebrolysin

Cinnarizin (stugeron)